Stewardship-Guided T2Candida Testing Shortens Time to Antifungal Treatment and Reduces Antifungal Usage Among Medical Intensive Care Unit Patients With Septic Shock.

Background: Diagnosis of invasive candidiasis (IC) is limited by insensitivity and slow turnaround of cultures. Our objectives were to define the performance of T2Candida, a nonculture test, under guidance of a diagnostic stewardship program, and evaluate impact on time to antifungal initiation and antifungal utilization. Methods: This was a retrospective study of adult medical intensive care unit (MICU) patients with septic shock for whom T2Candida testing was performed from March 2017 to March 2020. Patients with positive T2Candida results during this period were compared to MICU patients who did not undergo T2Candida testing but had septic shock and blood cultures positive for Candida from January 2016 through March 2020. Results: Overall, 155 T2Candida tests from 143 patients were included. Nine percent of T2Candida tests were positive compared to 4.5% of blood cultures. Sensitivity, specificity, positive predictive value, and negative predictive value of T2Candida for proven and probable IC were 78%, 95%, 50%, and 99%, respectively. Patients who tested positive for T2Candida (n = 14) were diagnosed earlier and initiated on antifungal therapy sooner than patients with IC (n = 14) diagnosed by blood culture alone (median, 5.6 vs 60 hours; P < .0001). Median antifungal days of therapy/1000 patient-days were 23.3/month preimplementation and 15/month postimplementation (P  = .007). Following a negative T2Candida result, empiric antifungals were either not administered in 58% or discontinued within 72 hours in 96% of patients. Conclusions: Diagnostic stewardship guided T2Candida testing resulted in reduced time to IC diagnosis, faster initiation of antifungal therapy, and lower antifungal usage among MICU patients with septic shock.

Case presentations of medication management for patients at risk for drug-associated acute kidney injury identified with a CDS system and a novel biomarker.

PURPOSE: Traditional methods used to evaluate changes in kidney function to identify acute kidney injury (AKI) have significant limitations. Damage biomarkers can identify patients at risk for AKI prior to changes in kidney function. While clinical trials have shown that biomarker-guided treatment can improve outcomes, whether these biomarkers can influence providers' choice of treatment strategy for risk prediction, surveillance, or diagnostic evaluation in clinical practice is uncertain. SUMMARY: This case series describes 4 patients at an academic medical center whose care was informed by kidney biomarker utilization in conjunction with a clinical decision support system (CDSS). Though each patient's clinical presentation was unique, kidney biomarkers were successfully employed as clinical tools in evaluating the risks and benefits of nephrotoxic medications. CONCLUSION: This case series demonstrates 4 scenarios in which a kidney injury biomarker used in conjunction with CDSS and consideration of the patients' clinical presentation informed treatment strategies with the intent to prevent AKI.

Interventions, Barriers, and Proposed Solutions Associated With the Implementation of a Protocol That Uses Clinical Decision Support and a Stress Biomarker Test to Identify ICU Patients at High-Risk for Drug Associated Acute Kidney Injury.

BACKGROUND: Damage biomarkers are helpful in early identification of patients who are at risk of developing acute kidney injury (AKI). Investigations are ongoing to identify the optimal role of stress/damage biomarkers in clinical practice regarding AKI risk prediction, surveillance, diagnosis, and prognosis. OBJECTIVE: To determine the impact of utilizing a clinical decision support system (CDSS) to guide stress biomarker testing in intensive care unit (ICU) patients at risk for drug-induced acute kidney injury (D-AKI). METHODS: A protocol was designed utilizing a clinical decision support system (CDSS) alert to identify patients that were ordered 3 or more potentially nephrotoxic medications, suggesting risk for progressing to AKI from nephrotoxic burden. Once alerted to these high-risk patients, the pharmacist determined if action was needed by ordering a stress biomarker test, tissue inhibitor of metalloproteinase-2-insulin-like growth factor-binding protein 7 (TIMP-2•IGFBP7). If the biomarker test result was elevated, the pharmacist provided nephrotoxin stewardship recommendations to the team. Pharmacists recorded the response to the clinical decision support alert, ordering, and interpreting the TIMP-2•IGFBP7, and information regarding clinical interventions. An alert in conjunction with TIMP-2•IGFBP7 as a strategy for AKI risk prediction and stimulant for patient care management was assessed. In addition, barriers and solutions to protocol implementation were evaluated. RESULTS: There were 394 total activities recorded by pharmacists for 345 unique patients. Ninety-three (93/394; 23.6%) actionable alerts resulted in a TIMP-2•IGFBP7 test being ordered. Thirty-one TIMP-2•IGFBP7 results were >0.3 (31/81; 38.3%), suggesting a high-risk of progression to AKI, which prompted 191 pharmacist/team interventions. On average, there were 1.64 interventions per patient in the low-risk patients, 3.43 in high-risk patients, and 3.75 in the highest-risk patients. CONCLUSION AND RELEVANCE: Stress biomarkers can be used in conjunction with CDSS alerts to affect therapeutic decisions in ICU patients at high-risk for D-AKI.

Peripherally Infused Norepinephrine to Avoid Central Venous Catheter Placement in a Medical Intensive Care Unit: A Pilot Study.

BACKGROUND: Reducing central venous catheter (CVC) utilization can reduce complications in the intensive care unit (ICU). While norepinephrine (NE) is traditionally administered via a CVC, lower concentrations may be safely administered via peripheral intravenous (PIV) lines. OBJECTIVE: We aimed to describe the implementation of a pilot protocol utilizing PIVs to administer a low-dose and lower-concentration NE, review the number of CVCs avoided, and evaluate any adverse events. METHODS: In a quaternary medical intensive care unit (MICU), from March 1, 2019, to February 29, 2020, we reviewed charts for CVC placement and adverse events from the pNE infusion. We also measured unit-level CVC utilization in all MICU patients and assessed the change in utilization associated with the peripheral norepinephrine (pNE) protocol. RESULTS: Over a 1-year period, 87 patients received a pNE infusion. Overall, 44 patients (51%) never required CVC placement during their MICU stay. Three patients (3%) experienced adverse events, none of which were documented as serious and or required antidote for treatment. Implementation of the protocol was associated with a decrease in the number of patients at the unit level who received CVCs, even if they did not receive pNE. CONCLUSION AND RELEVANCE: In this small pilot study, we pragmatically demonstrated that pNE is safe and may reduce the need for CVC placement. This information can be used to aid in pNE protocol development and implementation at other institutions, but further research should be done to confirm the safety of routine use of pNE in clinical practice.

Comparison of three cisatracurium dosing strategies in acute respiratory distress syndrome: A focus on drug utilization and improvement in oxygenation.

PURPOSE: Three continuous dosing strategies of cisatracurium (CIS) for acute respiratory distress syndrome (ARDS) have been described in the literature. After implementation of a ventilator synchrony protocol (VSP), we sought to determine which continuous CIS dosing strategy utilized the least amount of drug without compromising efficacy. METHODS: We retrospectively reviewed patients with ARDS receiving continuous CIS from January 1, 2013 to December 31, 2018. We categorized patients into one of three dosing strategies: fixed dose (FD), titration based solely on train-of-four (TOF), or the VSP. We documented drug consumption and determined efficacy by comparing the change in PaO2/FiO2 ratio (P/F) and oxygenation index (OI) from baseline up to 48 h. RESULTS: A total of 1047 patients were screened, and 189 met inclusion criteria (VSP = 69, TOF = 99, FD = 21). Drug consumption (mg) was significantly lower in the VSP arm: 415 [IQR 318-528] compared to both the TOF: 665 [IQR 472-927] and the FD arms: 1730 [IQR 1695-1800], p < 0.001 for each. The change in P/F and OI from baseline were statistically equivalent at all time points. CONCLUSION: Without impacting efficacy of gas exchange, a protocol using ventilator synchrony for CIS titration required significantly less drug compared to TOF-based titration and a fixed dosing regimen.

Impact of benzodiazepines on time to awakening in post cardiac arrest patients.

AIM: Although guidelines recommend use of short acting sedation after cardiac arrest, there is significant practice variation. We examined whether benzodiazepine use is associated with delayed awakening in this population. METHODS: We performed a retrospective single center study including comatose patients treated after in- or out-of-hospital cardiac arrest from January 2010 to September 2019. We excluded patients who awakened within 6 h of arrest, those who arrested due to trauma or neurological event, those with nonsurvivable primary brain injury and those with refractory shock. Our primary exposure of interest was high-dose benzodiazepine (>10 mg of midazolam equivalents per day) administration in the first 72-h post arrest. Our primary outcome was time to awakening. We used Cox regression to test for an independent association between exposure and outcome after controlling for biologically plausible covariates. RESULTS: Overall, 2778 patients presented during the study period, 621 met inclusion criteria and 209 (34%) awakened after a median of 4 [IQR 3-7] days. Patients who received high-dose benzodiazepines awakened later than those who did not (5 [IQR 3-11] vs. 3 [IQR 3-6] days, P = 0.004). In adjusted regression, high-dose benzodiazepine exposure was independently associated with delayed awakening (adjusted hazard ratio 0.63 (95% CI 0.43-0.92)). Length of stay, awakening to discharge, and duration of mechanical ventilation were similar across groups. CONCLUSION: High-dose benzodiazepine exposure is independently associated with delayed awakening in comatose survivors of cardiac arrest.

An Evaluation of Continuous Infusion Rocuronium for Sustained Neuromuscular Blockade in Critically Ill Adults.

BACKGROUND: Recent medication shortages of the neuromuscular blocking agent (NMBA) cisatracurium have forced the prescribing of aminosteroidal agents such as rocuronium. There are limited data on the use and dosing of continuous infusion (CI) rocuronium in critically ill patients outside of the operating room. OBJECTIVE: We sought to describe the use of CI rocuronium for sustained neuromuscular blockade in intensive care unit (ICU) patients by characterizing the dosing, utilization, and safety profile in patients with multiple organ failure (MOF) and non-MOF. METHODS: This was a retrospective review of patients in mixed ICUs from 2 tertiary medical centers who received CI rocuronium between January 2018 and July 2019. RESULTS: A total of 46 unique rocuronium infusions were utilized for 40 patients during the evaluation period. Of these, 37% had MOF, and 41% had at least 1 organ fail during the rocuronium infusion. The median starting and maximum dose was 8 µg/kg/min. Overall, 64% of train of 4 (TOF) measurements were a TOF 0 (T0) or TOF 1 (T1), with a higher percentage of T0 or T1 in the MOF group compared with the non-MOF group (75% vs 50%). The median time to recovery was more than twice as long for the MOF compared with the non-MOF group (10 vs 4.6 hours). ICU-acquired weakness was diagnosed in 27% of survivors. CONCLUSION AND RELEVANCE: In ICU patients with MOF, continuous rocuronium infusions were associated with deep levels of paralysis and prolonged recovery times. If neuromuscular blockade is required for critically ill patients, alternative strategies could be considered.

A Quality Improvement Evaluation of a Primary As-Needed Light Sedation Protocol in Mechanically Ventilated Adults.

OBJECTIVES: First, to implement successfully a light-sedation protocol, favoring initial as-needed (prioritizing as-needed) boluses over continuous infusion sedation, and second, to evaluate if this protocol was associated with differences in patient-level sedative requirements, clinical outcomes, and unit-level longitudinal changes in pharmacy charges for sedative medications. DESIGN: Retrospective review comparing patients who received the prioritizing as-needed sedation protocol to similar patients eligible for the prioritizing as-needed protocol but treated initially with continuous infusion sedation. SETTING: Thirty-two bed medical ICUs in a large academic medical center. PATIENTS: A total of 254 mechanical ventilated patients with a target Riker Sedation-Agitation Scale goal of 3 or 4 were evaluated over a 2-year period. Of the evaluable patients, 114 received the prioritizing as-needed sedation protocol and 140 received a primary continuous infusion approach. INTERVENTIONS: A multidisciplinary leadership team created and implemented a light-sedation protocol, focusing on avoiding initiation of continuous sedative infusions and prioritizing prioritizing as-needed sedation. MEASUREMENTS AND MAIN RESULTS: Overall, 42% of patients in the prioritizing as-needed group never received continuous infusion sedation. Compared with the continuous infusion sedation group, patients treated with the prioritizing as-needed protocol received significantly less opioid, propofol, and benzodiazepine. Patients in the prioritizing as-needed group experienced less delirium, shorter duration of mechanical ventilation, and shorter ICU length of stay. Adverse events were similar between the two groups. At the unit level, protocol implementation was associated with reductions in the use of continuous infusion sedative medications. CONCLUSIONS: Implementation and use of a prioritizing as-needed protocol targeting light sedation appear to be safe and effective. These single-ICU retrospective findings require wider, prospective validation.

Use of tissue inhibitor of metalloproteinase 2 and insulin-like growth factor binding protein 7 [TIMP2]•[IGFBP7] as an AKI risk screening tool to manage patients in the real-world setting.

PURPOSE: To determine the application of various components of the Kidney Disease Improving Global Outcomes (KDIGO) bundle in managing patients at high-risk for AKI progression ([TIMP2]•[IGFBP7] >0.3) in the real-world setting. METHODS: Patients with a [TIMP2]•[IGFBP7] test ordered between 5/23/16-2/28/18 were evaluated. We reviewed the medical record for evidence of implementation of the KDIGO bundle in response to biomarker test results. Evidence including explicit documentation in physicians' note discussing [TIMP2]•[IGFBP7] results and implicit evidence from review of dose adjusted medications, discontinued nephrotoxins and therapeutic drug monitoring. RESULTS: 105 [TIMP2]•[IGFBP7] tests were conducted in 100 patients (54% female; mean age 55.4 ± 16.8; 89% in the ICU). Sixty-one patients had a value of >0.3 and 46 (75.4%) of these patients received at least one management strategy consistent with KDIGO. By contrast, nine patients (23.1%) with [TIMP2]•[IGFBP7] ≤0.3 received one or more components of the KDIGO bundle (p < .001). CONCLUSION: In a real-world setting the use of urinary [TIMP2]•[IGFBP7] as an AKI risk screening tool resulted in differential application of various components of the KDIGO bundle for patient management for those with a positive test result.

Apixaban or Rivaroxaban Versus Warfarin for Treatment of Submassive Pulmonary Embolism After Catheter-Directed Thrombolysis.

BACKGROUND: Little data exist on the use of direct oral anticoagulant (DOAC) factor Xa inhibitors for submassive pulmonary embolism (PE) after catheter-directed thrombolysis (CDT). The objective of this evaluation was to determine whether the transition from parenteral anticoagulation to DOACs for submassive PE after CDT would decrease hospital length of stay (LOS) compared to warfarin. METHODS: A retrospective review of patients diagnosed with submassive PE who underwent CDT was conducted from January 1, 2012, to February 28, 2017. Hospital LOS and major and minor bleeding events were recorded during hospitalization and at 90 days. RESULTS: Sixty-two patients met the inclusion criteria, 36 in warfarin group and 26 in the DOAC group. Overall, patients receiving rivaroxaban or apixaban had a shorter median hospital LOS compared to warfarin (4.0 vs 6.1 days, P = .002). In the multivariate regression analysis, administration of DOAC was an independent predictor of decreased hospital LOS, ß: -2.1, 95% confidence interval (-3.5 to -0.7). CONCLUSION: Among patients with submassive PE, initiation of a DOAC shortly after CDT may result in a decreased hospital LOS compared to parenterally bridged warfarin.

Ketamine Infusion for Adjunct Sedation in Mechanically Ventilated Adults.

BACKGROUND: Many critically ill patients receive ketamine for adjunct sedation despite a paucity of evidence on its use, dosing, and monitoring in this setting. OBJECTIVE: To describe the dosing and safety considerations of ketamine for adjunct sedation in a population of mechanically ventilated critically ill patients targeting light sedation. METHODS: We conducted a retrospective review of mechanically ventilated patients receiving continuous ketamine infusion between January 2012 and April 2016. Data included dosing, effect of ketamine on other sedatives, total sedative use, Riker Sedation-Agitation Scale (SAS) scores, adverse drug reactions (ADRs), and hemodynamic variables. RESULTS: Ninety-one patients were included in the analysis. Ketamine was infused at a median dosage of 0.41 mg/kg/hour (range 0.04-2.5 mg/kg/hr) for up to 14.7 days (median 2.8 days). Concomitant sedatives were reduced or discontinued, without the initiation of an additional sedative, in 57 patients (63%) within 24 hours of initiating ketamine. Propofol was most commonly discontinued (16 patients, 36%), followed by benzodiazepines (12 patients, 27%). There was an increase in the number of SAS scores documented in goal in the 24-hour period after ketamine initiation compared with the immediate 24 hours before (61% vs 55%, p=0.001). Patients were less frequently agitated, defined as SAS >4, after the initiation of ketamine (27% vs 33%, p=0.005). Seven patients (7.7%) required discontinuation of ketamine infusion for an ADR. There were no significant changes in hemodynamic variables after the initiation of ketamine. CONCLUSIONS: Continuous ketamine infusion for adjunct light sedation was well tolerated in a cohort of critically ill adults, with an acceptable safety profile. Prospective studies of ketamine infusion are warranted to further establish its efficacy as a sedative in this population.

Association Between Train-of-Four Values and Gas Exchange Indices in Moderate to Severe Acute Respiratory Distress Syndrome.

BACKGROUND: Acute respiratory distress syndrome (ARDS) is associated with a mortality rate of approximately 40%. Neuromuscular blockade is associated with an improvement in oxygenation and a reduction in mortality in ARDS. OBJECTIVE: The goal of this evaluation was to determine if the depth of paralysis, determined by train-of-four (TOF) monitoring, correlates with gas exchange in moderate to severe ARDS. METHODS: This was a retrospective review of moderate to severe ARDS patients who were prescribed >12 hours of continuous infusion cisatracurium between January 1, 2013, and December 31, 2014, with a PaO2:FiO2 ratio <150 and documented TOF and arterial blood gases. Patients were evaluated for inclusion at 12, 24, and 48 hours after initiation of neuromuscular blockade. RESULTS: A total of 378 patients were screened for inclusion, with 107 evaluable patients meeting criteria at baseline. Poor correlation existed between TOF and oxygenation index (OI) at 12 (τ = 0.03), 24 (τ = 0.15) and 48 hours (τ = 0.08). When controlling for proning and baseline OI, the depth of paralysis did not have a significant effect on OI at 12, 24, or 48 hours. CONCLUSIONS: This evaluation demonstrates that the use of TOF monitoring for neuromuscular blockade does not correlate with gas exchange markers in moderate to severe ARDS.